The Kearns-Shy syndrome: A multisystem disease with mitochondrial abnormality demonstrated in skeletal muscle and skin

Abstract

An 11-year-old girl presented with external ophthalmoplegia and lid ptosis, pigmentary degeneration of the retina, complete heart block, skeletal muscle weakness, cerebellar deficit, stunted physical growth, fatigue and some mental subnormality. Total protein and IgM, IgA and IgG immunoglobulins were increased in the cerebrospinal fluid. Histochemical studies on the gastrocnemius and quadriceps muscle biopsies revealed many abnormal histochemical type I fibres in which excessive amounts of granular material having strong oxidative enzyme activity were prominent. On electron microscopy these muscle cells contained clusters of many abnormally large mitochondria in which the normal arrangement of the cristae was disturbed, the matrix was increased and sometimes contained dense deposits, and crystalloids were present in the intracristal space. Analogous mitochondrial abnormalities were present in many secretory cells of eccrine sweat glands in a skin biopsy. In skeletal muscle excessive lipid droplets (presumably glycerides) were present close to the abnormal mitochondria. Many patients exhibiting the main clinical and laboratory features of our patient have been recognized and reported in the literature. A clinically identifiable entity emerges which we propose to designate the Kearns-Shy syndrome. While the described mitochondrial abnormalities in muscle cells are not found only in this syndrome, their demonstration is useful in confirmation of the diagnosis, since they have been observed in all cases of the syndrome where muscle biopsies were studied by histochemistry and electron microscopy. Mitochondrial alterations have also been reported in liver cells, cerebellar cortical cells and extraocular muscle fibres. The relationship between the mitochondrial abnormalities and the disturbed tissue function remains obscure. The aetiology of this disorder is unknown; there has been no documented familial occurrence to suggest a genetically determined process.